Background

The clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury.

Methods

We evaluated the characteristics and clinical course of immune-related liver injury in 1214 patients treated with ICIs for advanced malignancies except for hepatocellular carcinoma between August 2014 and May 2021.

Results

During the follow-up period (median, 252 days), 58 patients (4.8%) had an immune-related liver injury (≥ Grade 3). The liver-injury patterns were hepatocellular (n = 26, 44.8%), mixed (n = 11, 19.0%), or cholestatic (n = 21, 36.2%), and the median time to onset of liver injury was 39, 81, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (p = 0.047). Corticosteroids were administered to 30 (51.7%) patients; while liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns, and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20.

Conclusion

The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differ according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

中文翻译：

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免疫检查点抑制剂致晚期恶性肿瘤患者肝损伤的临床过程

背景

免疫检查点抑制剂（ICIs）引起的肝损伤的临床病程因人而异，很少有关于基于肝损伤模式的皮质类固醇治疗效果的报道。

方法

我们评估了 2014 年 8 月至 2021 年 5 月期间接受 ICI 治疗的晚期恶性肿瘤（肝细胞癌除外）的 1214 例免疫相关肝损伤的特征和临床病程。

结果

在随访期间（中位数，252 天），58 名患者（4.8%）出现免疫相关肝损伤（≥ 3 级）。肝损伤模式为肝细胞 ( n  = 26, 44.8%)、混合 ( n  = 11, 19.0%) 或胆汁淤积 ( n  = 21, 36.2%)，肝损伤发生的中位时间为 39, 81 , 和 53 天，分别；肝细胞模式发生的时间早于其他类型（p  = 0.047）。30 名 (51.7%) 患者接受了皮质类固醇治疗；而几乎所有肝细胞型患者的肝损伤都有所改善（n = 13/14, 92.9%)，超过一半的非肝细胞型患者未能显示改善，3 名混合型患者需要使用霉酚酸酯进行二次免疫抑制。对 13 名患者进行的肝活检主要显示小叶损伤、内皮炎和点状坏死，并伴有 CD3 和 CD8 阳性的 T 细胞浸润，但没有 CD4 或 CD20。

结论

免疫相关性肝损伤中皮质类固醇的发生率模式和治疗反应因损伤类型而异。尽管皮质类固醇对肝细胞模式有效，但需要针对难治性非肝细胞模式的额外策略。